Bump: I just experienced the same problem. I run a number of web servers (Windows Server 2008 SP2 Web Edition) that all use IIS6's built in SMTP server to relay email. All the boxes rely on a common instance of SQL Server.

A few days ago, we restarted the SQL Server, so the sites started throwing errors - which obviously couldn't be logged to the database. As a fail safe, we have the sites send the error emails to an admin email address.

We then restarted each web server only to notice that no email is being delivered. My investigation has revealed that none of the SMTP configuration has been retained.

Do I really have to redo this for every server every time I restart? How can this configuration loss be prevented?

This may not be the case, but I found that the SMTP service on Server 2008 is set to Manual startup by default after installing the role. So when we rebooted several 2008 Servers the service was stopped. Ensure it's set to Automatic within Services.